Hutson T H, Kathe C, Moon L D F
Centre for Restorative Neuroscience, Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.
Neurorestoration Group, Wolfson Centre for Age-Related Diseases, King's College London, London, UK.
Gene Ther. 2016 Feb;23(2):231-6. doi: 10.1038/gt.2015.103. Epub 2015 Dec 10.
Adeno-associated viral (AAV) vectors are one of the most promising gene delivery systems to the central nervous system. We now report, that AAV1 can be used to express transgenes trans-neuronally in neurons distant from the injection site. Specifically, intracortical injection of a bicistronic AAV1 vector trans-neuronally transduced spinal neurons as shown by fluorescence microscopy, the presence of AAV genome and AAV transcript in the contralateral spinal cord. Prior pyramidotomy abolished spinal transduction, confirming anterograde axonal transport of AAV1 in the corticospinal tract. These observations demonstrate the potential of bicistronic AAV1 for trans-neuronal expression of therapeutic transgenes in neurological disorders or reporter genes in connectivity studies.
腺相关病毒(AAV)载体是向中枢神经系统递送基因最有前景的系统之一。我们现在报告,AAV1可用于在远离注射部位的神经元中跨神经元表达转基因。具体而言,如荧光显微镜所示,脑内注射双顺反子AAV1载体可跨神经元转导脊髓神经元,对侧脊髓中存在AAV基因组和AAV转录本。先前的锥体切断术消除了脊髓转导,证实了AAV1在皮质脊髓束中的顺行轴突运输。这些观察结果证明了双顺反子AAV1在神经疾病中治疗性转基因的跨神经元表达或连接性研究中报告基因表达方面的潜力。